β1 Integrins Modulate Cell Adhesion by Regulating Insulin-Like Growth Factor-II Levels in the Microenvironment
| Autor: | Lucia R. Languino, Loredana Moro, Hira Lal Goel, Natalia Teider, Thomas L. McCarthy, Albert J. Wong, Michael Centrella, Ersilia Marra, Michael King, Marina Holgado-Madruga |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Cytoplasm Cancer Research medicine.medical_specialty Integrin Protein Tyrosine Phosphatase Non-Receptor Type 11 CHO Cells Transfection Extracellular matrix Mice Phosphatidylinositol 3-Kinases Insulin-Like Growth Factor II Cricetinae Internal medicine Cell Adhesion medicine Animals Humans Protein Phosphatase 2 RNA Messenger Autocrine signalling Cell adhesion Adaptor Proteins Signal Transducing Tumor microenvironment biology Cell adhesion molecule Cell growth Integrin beta1 Intracellular Signaling Peptides and Proteins Prostatic Neoplasms Phosphoproteins Protein Structure Tertiary Up-Regulation Cell biology Endocrinology Oncology Cancer cell biology.protein Laminin Protein Tyrosine Phosphatases |
| Zdroj: | Cancer Research. 66:331-342 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-05-2588 |
| Popis: | The interactions between cancer cells and the extracellular matrix (ECM) regulate cancer progression. The β1C and β1A integrins, two cytoplasmic variants of the β1 integrin subfamily, are differentially expressed in prostate cancer. Using gene expression analysis, we show here that the β1C variant, an inhibitor of cell proliferation, which is down-regulated in prostate cancer, up-regulates insulin-like growth factor-II (IGF-II) mRNA and protein levels. In contrast, β1A does not affect IGF-II levels. We provide evidence that β1C-mediated up-regulation of IGF-II levels increases adhesion to Laminin-1, a basement membrane protein down-regulated in prostate cancer, and that the β1C cytoplasmic domain contains the structural motif sufficient to increase cell adhesion to Laminin-1. This autocrine mechanism that locally supports cell adhesion to Laminin-1 via IGF-II is selectively regulated by the β1 cytoplasmic domain via activation of the growth factor receptor binding protein 2–associated binder-1/SH2-containing protein-tyrosine phosphatase 2/phosphatidylinositol 3-kinase pathway. Thus, the concurrent local loss of β1C integrin, of its ligand Laminin-1, and of IGF-II in the tumor microenvironment may promote prostate cancer cell invasion and metastasis by reducing cancer cell adhesive properties. It is, therefore, conceivable that reexpression of β1C will be sufficient to revert a neoplastic phenotype to a nonproliferative and highly adherent normal phenotype. (Cancer Res 2006; 66(1): 331-42) |
| Databáze: | OpenAIRE |
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